Pharmacokinetic drug-drug interaction between the COVID-19 3CL protease inhibitor GST-HG171 and itraconazole in healthy subjects

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ABSTRACT GST-HG171 (also known as atilotrelvir) is a novel, orally administered 3CL protease inhibitor approved in China for treating mild-to-moderate COVID-19. In this study, we assessed the drug-drug interaction between GST-HG171 (boosted with ritonavir) and itraconazole (a strong CYP3A inhibitor) in healthy Chinese adult volunteers. A total of 12 healthy subjects were enrolled in this two-period study. In period 1, all subjects received 150 mg GST-HG171/100 mg ritonavir twice daily (BID) on Days 1–3 (with a single dose on Day 3); after a 5-day washout period, subjects proceeded to period 2. In period 2, subjects orally took 200 mg itraconazole once daily (QD) on Days 8–16. On Days 12–14, subjects were co-administered 150 mg GST-HG171/100 mg ritonavir (BID, with a single dose on Day 14) and itraconazole. Serial blood samples were collected after administration of GST-HG171/ritonavir alone and co-administration of itraconazole for the measurement of pharmacokinetic parameters. Co-administration of itraconazole with GST-HG171/ritonavir resulted in a mild increase in the C max of GST-HG171 and ritonavir by approximately 8% and 28%, respectively, while systemic exposure (area under the plasma concentration-time curve [AUC]) was elevated by approximately 45% and 33%, respectively. There was no apparent increase in the incidence or severity of AEs during the co-administration period. In conclusion, co-administration of itraconazole, a strong CYP3A4 inhibitor, with GST-HG171/ritonavir resulted in a moderate increase in exposure of GST-HG171 and mild increase in exposure of ritonavir, and it had an acceptable safety profile and was well tolerated in this study. CLINICAL TRIALS This study is registered with ClinicalTrials.gov as NCT06087055 .

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